Features of Muon Arrival Time Distributions of High Energy EAS at Large Distances From the Shower Axis

In view of the current efforts to extend the KASCADE experiment (KASCADE-Grande) for observations of Extensive Air Showers (EAS) of primary energies up to 1 EeV, the features of muon arrival time distributions and their correlations with other observable EAS quantities have been scrutinised on basis of high-energy EAS, simulated with the Monte Carlo code CORSIKA and using in general the QGSJET model as generator. Methodically various correlations of adequately defined arrival time parameters with other EAS parameters have been investigated by invoking non-parametric methods for the analysis of multivariate distributions, studying the classification and misclassification probabilities of various observable sets. It turns out that adding the arrival time information and the multiplicity of muons spanning the observed time distributions has distinct effects improving the mass discrimination. A further outcome of the studies is the feature that for the considered ranges of primary energies and of distances from the shower axis the discrimination power of global arrival time distributions referring to the arrival time of the shower core is only marginally enhanced as compared to local distributions referring to the arrival of the locally first muon.Comment: 24 pages, Journal Physics G accepte

The JCMT Plane Survey: First complete data release - emission maps and compact source catalogue

We present the first data release of the James Clerk Maxwell Telescope (JCMT) Plane Survey (JPS), the JPS Public Release 1 (JPSPR1). JPS is an 850-µm continuum survey of six fields in the northern inner Galactic Plane in a longitude range of ℓ = 7°–63°, made with the Sub-millimetre Common-User Bolometer Array 2 (SCUBA-2). This first data release consists of emission maps of the six JPS regions with an average pixel-to-pixel noise of 7.19 mJy beam−1, when smoothed over the beam, and a compact-source catalogue containing 7,813 sources. The 95 per cent completeness limits of the catalogue are estimated at 0.04 Jy beam−1 and 0.3 Jy for the peak and integrated flux densities, respectively. The emission contained in the compact-source catalogue is 42 ± 5 per cent of the total and, apart from the large-scale (greater than 8 arcmin) emission, there is excellent correspondence with features in the 500-µm Herschel maps. We find that, with two-dimensional matching, 98 ± 2 per cent of sources within the fields centred at ℓ = 20°, 30°, 40° and 50° are associated with molecular clouds, with 91 ± 3 per cent of the ℓ = 30° and 40° sources associated with dense molecular clumps. Matching the JPS catalogue to Herschel 70-µm sources, we find that 38 ± 1 per cent of sources show evidence of ongoing star formation. The images and catalogue will be a valuable resource for studies of star formation in the Galaxy and the role of environment and spiral arms in the star formation process

Shelled pteropods in peril: Assessing vulnerability in a high CO2 ocean

The impact of anthropogenic ocean acidification (OA) on marine ecosystems is a vital concern facing marine scientists and managers of ocean resources. Euthecosomatous pteropods (holoplanktonic gastropods) represent an excellent sentinel for indicating exposure to anthropogenic OA because of the sensitivity of their aragonite shells to the OA conditions less favorable for calcification. However, an integration of observations, experiments and modelling efforts is needed to make accurate predictions of how these organisms will respond to future changes to their environment. Our understanding of the underlying organismal biology and life history is far from complete and must be improved if we are to comprehend fully the responses of these organisms to the multitude of stressors in their environment beyond OA. This review considers the present state of research and understanding of euthecosomatous pteropod biology and ecology of these organisms and considers promising new laboratory methods, advances in instrumentation (such as molecular, trace elements, stable isotopes, palaeobiology alongside autonomous sampling platforms, CT scanning and high-quality video recording) and novel field-based approaches (i.e. studies of upwelling and CO2 vent regions) that may allow us to improve our predictive capacity of their vulnerability and/or resilience. In addition to playing a critical ecological and biogeochemical role, pteropods can offer a significant value as an early-indicator of anthropogenic OA. This role as a sentinel species should be developed further to consolidate their potential use within marine environmental management policy making

Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis

Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Systemic Lupus Erythematosus: State of the Art on Clinical Practice Guidelines

Systemic lupus erythematosus (SLE) is the paradigm of systemic autoimmune diseases characterised by a wide spectrum of clinical manifestations with an unpredictable relapsing-remitting course. The aim of the present work was to identify current available clinical practice guidelines (CPGs) for SLE, to provide their review and to identify physicians' and patients' unmet needs. Twenty-three original guidelines published between 2004 and 2017 were identified. Many aspects of disease management are covered, including global disease management, lupus nephritis and neuropsychiatric involvement, management of pregnancies, vaccinations and comorbidities monitoring. Unmet needs relate with disease management of some clinical manifestations and adherence to treatment. Many patient's unmet needs have been identified starting with faster diagnosis, need for more therapeutic options, guidelines on lifestyle issues, attention to quality of life and adequate education.info:eu-repo/semantics/publishedVersio

Pharmacologically Reversible, Loss of Function Mutations in the tm2 and tm4 Inner Pore Helices of Trek-1 k2p Channels

A better understanding of the gating of TREK two pore domain potassium (K2P) channels and their activation by compounds such as the negatively charged activator, flufenamic acid (FFA) is critical in the search for more potent and selective activators of these channels. Currents through wild-type and mutated human K2P channels expressed in tsA201 cells were measured using whole-cell patch-clamp recordings in the presence and absence of FFA. Mutation of the TM2.6 residue of TREK-1 to a phenylalanine (G171F) and a similar mutation of TM4.6 (A286F) substantially reduced current through TREK-1 channels. In complementary experiments, replacing the natural F residues at the equivalent position in TRESK channels, significantly enhanced current. Known, gain of function mutations of TREK-1 (G137I, Y284A) recovered current through these mutated channels. This reduction in current could be also be reversed pharmacologically, by FFA. However, an appropriate length MTS (MethaneThioSulfonate) cross-linking reagent (MTS14) restricted the activation of TREK-1_A286C channels by repeated application of FFA. This suggests that the cross-linker stabilises the channel in a conformation which blunts FFA activation. Pharmacologically reversible mutations of TREK channels will help to clarify the importance of these channels in pathophysiological conditions such as pain and depression